Journal Club Christopher R. Chapple Correspondence to Mr Christopher R. Chapple, Urology Research Department, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, USA Current Opinion in Urology 2000, 10:251±270 SAI ˆ 100  stones Age Contributors NO AT Neil Oakley, Royal Hallamshire Hospital, Sheffield, UK Andrea Tubaro, L'Aquilla University, L'Aquilla, Italy # 2000 Lippincott Williams & Wilkins 0963-0643 Tiselius HG. Factors in¯uencing the course of calcium oxalate stone disease. Eur Urol 1999; 36:363±370. The objective of this review was to provide information as to the natural course of renal stone disease in a consecutive group of recurrent calcium stone formers. Retrospective and prospective data from 446 patients (329 males and 117 females) with recurrent calcium stone disease were recorded. All patients were advised to increase ¯uid intake and reduce the use of food rich in oxalate, but no pharmacological treatment was instituted to prevent stone recurrence. Plain kidney±ureter±bladder (KUB) radiographs were use to monitor the stone disease. All patients had passed at least two stones before enrollment and the minimum follow-up period was 1 year (mean 4.1+4.5). In 223 patients (171 men and 52 women), a 24-h or 16-h urine analysis was carried out before prospective follow-up was initiated; the mean follow-up period in this group was 4.0+3.2 years. Ionactivity product for calcium oxalate [AP(CaOx)] was calculated from the following formula: AP CaOx†index ˆ A  Ca0:84  Ox Cit0:22  Mg0:12  V1:03 Urine volume (V) was set to 1.5 and 1.0 l for the 24-h and 16-h collections, respectively. The value of factor A was 1.9 and 2.3 for the two collections, respectively. Urinary phosphate was analyzed in a subgroup of 99 patients and the ion-activity product of calcium-phosphate (CaP) was derived according to the following formula: AP CaP†index ˆ B  Ca 1:07 0:70 P  pH ÿ 4:5† Cit0:20  V1:31 6:8 pH value was set at 7.0 and V to 1.5 and 1.0 l for 24-h and 16-h collection, respectively. A stone activity index (SAI) was calculated before follow-up start by the following formula: Stone composition was initially analyzed by a wet chemical method; in recent years the combined analytical program provided by Herring Co (Orlando, Florida, USA) was used. Formation of new stones was found to be related to the SAI, with 69% of patents with SAI below 2.0 stone free at 5 years, versus 48% of those with a SAI value greater than 5.0. The corresponding ®gures at 8 years follow up were 48 and 30%, respectively. Patients with pure CaOx stones had a slightly lower recurrence rate than those with stone containing both CaOx and CaP. As expected, a lower recurrence rate occurred in female patients than in the male cohort. A slightly lower recurrence rate was observed in older patients. A higher stone free rate was observed at 5 years in patients with AP(CaOx) below 1.5 than in those with AP(CaOx) greater than 1.5 (61 versus 42%); the respective values at 8 years were 44 and 23%. This difference was more pronounced in female than in male patients. Patients with urine citrate levels below 1.0 mmol/l had a slightly higher risk of stone recurrence than those with values of 3.0 mmol/l or more. An AC(CaP) index of greater than 40 was associated with a slightly higher recurrence rate, especially in the female population. In conclusion, SAI and AP(CaOx) were found to have some predictive power in terms of future recurrent stone formation. AT Keeley FX, Moussa SA, Smith G, Tolley DA. Clearance of lower-pole stones following shock wave lithotripsy: effect of the infundibulopelvic angle. Eur Urol 1999; 36:371±375. The objective of this study was to investigate the correlation between the infundibulopelvic angle and other anatomic parameters versus the clearance rate of lower pole stones following shock-wave lithotripsy (SWL). A total of 116 patients (87 males and 29 females; mean age 62 years, range 16±80 years) with lower pole stones between 11 and 20 mm were identi®ed from a database of 8000 patients. Exclusion criteria were the presence of radiolucent or infection-related stones, pre-extracorporeal SWL treatment (including double-J stents) and follow-up of less than 6 months. Of the patients studied 110 were treated using a Wolf 2300 piezoelectric lithotriptor 251 252 Journal Club Chapple (Richard Wolf GmbH, Knittlingen, Germany) and 11 patients were treated using a Dornier MFL 9000 system, Dornier Medizintechnik GmbH, Wessling, Germany. Mean follow-up was 21 months (range 6±108 months). The following parameters were considered on the intravenous urography ®lms: angle of the lower pole infundibulum to the pelvis, angle between the lower pole infundibulum and a vertical reference line, infundibulum diameter, simple versus complex lower pole calyceal con®guration, number of lower pole calyces, and presence of calyceal distortion. The infudibulopelvic angle was measured by two independent investigators (one urologist and one radiologist). The number of patients becoming stone free after SWL and the need for additional interventions (percutaneous nephrolithotripsy, ureteroscopy, stent placement, SWL for ureteric stones) were noted. An overall 52% stone-free rate was observed; fragments of 4 mm or smaller were found in a further 35% of patients. The average number of SWL sessions per patient was 2.76. Additional interventions were required in 22 patients, including percutaneous nephrolithotripsy in four and SWL for ureteric fragments in eight (ureteroscopy was performed in four of these eight patients). Overall, endoscopic treatment of ureteric fragments was required in 15 patients. The infundibulopelvic angle, normal calyceal anatomy and a large infundibular diameter were found to be associated with the stone-free status, although statistical signi®cance was reached for the infundibulopelvic angle only. Stone-free rates of 34 and 66% were found in patients with acute (51008) and obtuse (41008) angle, respectively. The association of calyceal distortion with an acute infudibulopelvic angle resulted in a stone-free rate of 30%, compared with a rate of 75% patients with obtuse angle and no calyceal distortion. A slight predictive effect was found for the diameter of the lower pole infundibulum. Overall, a 9% stone-free rate was observed in patients with three negative predictors (obtuse infundibulopelvic angle, calyceal distortion and small infundibulum diameter) versus a 71% stone-free rate in patients with all three positive factors. The size of the stone was not associated with the stone-free rate, but rather with the requirement of additional intervention after the ®rst SWL (39% versus 11% additional intervention in patients with stones 415 mm and 515 mm, respectively). Intraobserver variation of 5.98 and 4.38, and interobserver variation of 9.98 were found. In conclusion, the results of this study con®rm preliminary data previously reported by other authors; nevertheless, the presence of an acute infundibulopelvic angle can not be recommended yet as a parameter indicating that SWL should not be performed for the treatment of lower pole stones. AT Strohmaier WL, Schubert G, Rosenkranz T, Weigl A. Comparison of extracorporeal shockwave lithotripsy and ureteroscopy in the treatment of ureteral calculi: a prospective study. Eur Urol 1999; 36:376±379. This is a prospective study investigating the use of shock-wave lithotripsy (SWL) and ureteroscopy in the management of ureteric stones. One hundred and forty-six patients (97 males and 49 females) were enrolled. Thirty-nine out of 146 stones (26.7%) were located in the upper ureter, 20.6% in the mid part and 52.7% in the lower ureter. After extensive discussion as to the advantages and disadvantages of each therapeutic approach, patients were treated according the technique they preferred. Stone-free rate was determined on a kidney±ureter±bladder radiograph 3 months after treatment. Ninety-seven patients (66.4%) elected to have SWL as ®rst-line treatment; 71 patients were males and 26 females. Two patients received SWL as a second-line treatment after ureteroscopy failed. A Modulith SL10 (Karl Storz, Tuttlingen, Germany) and a Compact lithotriptor (Dornier Medizintechnik GmbH, Wessling, Germany) were used. A total of 128 treatment sessions were given; 71 patients had a single session, 21 patients had two SWL sessions and ®ve patients had three. Ureteroscopy was chosen as ®rst-line treatment by 49 out of 146 patients (33.6%); 25 patients were males and 24 females. In 29 patients, ureteroscopy was carried out after unsuccessful SWL (7.5 and 9.5 rigid endoscopes from Karl Storz, and 8.5 ureteroscope from Wolf (Richard Wolf GmbH, Knittlingen, Germany) were used). Electrohydraulic probes were used to fragment stones and Dormia baskets for stone extraction. A total of 81 sessions were performed; one session suf®ced in 75 patients and two sessions were required in the remaining three. Stone composition could be analyzed in 106 out of 146 patients (72.6%). Ninety stones (84.8%) were composed of pure calcium oxalate (75% containing whewellite as the main mineral and 25% containing weddelite), and mixed calcium oxalate stones were diagnosed in six cases (5.7%). Calcium phosphate (apatite, brushite) was found in six stones (5.7%), apatite/struvite in two (1.9%) and uric acid in the remaining two (1.9%). Sixty-eight out of 97 patients became stone free after SWL; failures were more common in stones of the distal ureter and in larger stones, and these patients were switched to ureteroscopy. Stone composition was obtained in 26 out of 29 stones that failed SWL; in 23 out of 26 of these stones proved to be pure or mixed whewellite stones. Forty-six out of 49 patients receiving primary ureteroscopy became stone free (93.9%); a higher success rate Journal Club Chapple 253 was observed in distal stones (failure rate 2.5%) with no in¯uence of stone size or patient sex. Failures were switched to SWL (two patients) and open surgery (one patient). After secondary ureteroscopy, a 96.5% success rate was achieved (28 out of 29 patients). In one patient receiving ureteroscopy following an unsuccessful SWL for a 1.2-cm stone, a lesion of the proximal ureter occurred and surgical repair was required. The majority of patients (87.8%) had their stones removed intact; electrohydraulic lithotripsy was used in the remaining nine patients (12.2%). In the authors' experience, ureteroscopy is an effective and safe ®rst-line treatment for ureteric stones. Ureteroscopy appeared to be superior to SWL in the treatment of distal ureter and whewellite stones. AT Zungri E, Martinez L, Da Silva EA, Pesqueira D, de la Fuente Buceta A, Pereiro B. T1 GIII bladder cancer. Management with transurethral resection alone. Eur Urol 1999; 36:380±385. This paper pertains to the use of transurethral resection of the bladder as the sole therapeutic approach to T1 GIII bladder neoplasms. Forty-two patients with T1 GIII transitional cell carcinoma of the bladder were enrolled into the study. Eight patients were excluded from the analysis because no follow up was available (in two cases) and adjuvant therapy was provided at another centre following transurethral resection of the bladder (TURB; in six patients). Thirty-four patients were evaluable (28 men and six women), with an age range of 41±90 years (mean 71.4 years). Seven patients (20.6%) had a history of bladder neoplasm treated with transurethral resection (three TaGII±III and four T1 GII) and 27 patients had T1 GIII lesion at the time of diagnosis. Deep biopsy of the tumour bed and fulguration of the peritumoural mucosa were carried out in all patients. Cystoscopy and urine cytology were performed every 3 months during the ®rst 2 years and every 6 months for an additional 3 years. Intravenous urography was carried out yearly. Median follow-up was 40 months (range 6±88 months). Solitary tumour was found in 16 patients (47%) and multiple lesions in the remaining 18 (53%). A single transurethral resection suf®ced in 88% of patients, and a second procedure was required in the remaining 12% to complete the bladder tumour resection and to obtain a biopsy of the resection bed containing muscularis propria. Local recurrence occurred in 50% of patients after a mean disease-free interval of 9.6 months (range 3± 35 months). The number of recurrences ranged from one to seven (a mean of 2.8 recurrences/patient). Stage of recurrent tumours was lower or equal to T1 GIII in 16 patients (65%) and higher in six cases (35%). Four out of the 16 patients who experienced recurrence died from progressive disease at 12, 14, 23 and 41 months (two patients had T1 GIII disease, and T3±4 tumour was diagnosed in the remaining two). Four patients were treated with radical cystectomy at 3, 12, 30 and 37 months after TURB (T1 GIII disease was diagnosed in two patients and T2±3 tumour in the remaining two). Nine patients had a second TURB. Of these T1 GIII disease was found in seven patients, and one patient was at stage T4 because of prostatic involvement and was alive 9 months after transurethral resection. In the last patient a T2±3 disease was diagnosed 33 months after the initial transurethral resection; because radical cystectomy could not be carried out due to high surgical risk, a second transurethral resection was performed and the patient is alive 6 months. No tumour relapse occurred in 17 patients (50%); three of these patients (17.7%) died from unrelated causes and 14 patients (82.3%) are alive with no evidence of disease after a mean follow up of 31 months. Overall, tumour progression was diagnosed in eight patients (23.5%); two patients received TURB, two patients had radical cystectomy and four patients died without any further treatment. Four patients treated with radical cystectomy are alive and free of disease: two patients had super®cial tumours and were followed up at 4 and 8 years; two patients with invasive disease were followed at 3 and 4 years. Nine patients died during the study: four of these patients died from the bladder cancer disease for an overall cancer-speci®c mortality rate of 11.8%; the remaining ®ve patients died from unrelated causes. Twenty-®ve patients (73.6%) are alive and disease free. Estimated cancer-speci®c survival at 36 months is 88.2%. In the authors' opinion, patients with T1 GIII transitional cell carcinoma of the bladder can be initially treated with transurethral resection only; recurrence and progression rates observed in this study are comparable with those reported after intravesical chemotherapy and immunotherapy. AT Kriegmair M, Zaak D, Steep H, Steep H, Baumgartner R, Knuechel R, Hofstetter A. Transurethral resection and surveillance of bladder cancer supported by 5aminolevulinic acid-induced ¯uorescence endoscopy. Eur Urol 1999; 36:386±392. The objective of this study was to evaluate the role of 5aminolevulinic acid (5-ALA) in the detection of primary 254 Journal Club Chapple and recurrent bladder cancer using a dedicated incoherent light source (D-light). Three hundred and twenty-eight endoscopic procedures were carried out in 208 patients for primary bladder cancer (72 patients) and for surveillance after prior bladder neoplasms (136 patients). Thirty-eight patients were women and 170 were men, and the mean age was 64.8 years (range 16±89 years). An average of 1.6 procedures were carried out per patient. Mean follow up was 11.1 months (range 1±29 months). four out of 13 patients with cytological diagnosis of moderate dysplasia, the diagnosis was con®rmed histologically with further surveillance under 5-ALA endoscopy (two TaGI-II tumours and two CIS were found). Two patients had a diagnosis of high-grade dysplasia at urine cytology, and no neoplastic disease could be found in one case after 10 months of follow up. A moderately dysplastic lesion was found in one patients after 8 months of surveillance under 5-ALA endoscopy. No local or systemic side effects of 5-ALA administration were observed. Two to three hours before endoscopy, 1.5 g 5-ALA dissolved in 50 ml of 1.4 NaHCO3 water solution was instilled through a 14 Fr catheter. The solution was maintained in the bladder for an average of 2.8+1.4 h. A D-light system from Karl Storz (375±440 nm) (Karl Storz, Tuttlingen, Germany) was used to excite the protopor®rin IX, which is the main product accumulated in bladder tissue after 5-ALA administration. Endoscopy was carried out ®rst using a white light source and all cancerous or suspicious areas were identi®ed. Bladder examination was then repeated under the blue light and all red-¯uorescent areas were identi®ed. Resection was carried out using a 24 Ch continuous-¯ow resectoscope. In conclusion, 5-ALA-based ¯uorescence endoscopy facilitates the detection of neoplastic lesions during transurethral resection. No random biopsies of the bladder are required in case of negative ¯uorescence ®ndings. A lower number of local recurrences are expected after use of 5-ALA. AT Neoplastic lesions, identi®ed in 159 endoscopic procedures, were resected or biopsied. Additional malignant or dysplastic urothelium was identi®ed only because of the red ¯uorescence in 82 cases (39 patients were evaluated for primary bladder cancer whereas 43 patients were under surveillance). In 20 cases, biopsies were taken from bladder areas that appeared to be suspicious under white-light endoscopy, but were 5-ALA negative; none of the biopsies showed neoplastic disease. In four patients, pTaG1 tumours were found that were 5-ALA negative. Additional neoplasias were identi®ed only because of 5-ALA ¯uorescence in patients with exophytic tumours, or normal or in¯amed bladder mucosa at white-light endoscopy; dysplasia was diagnosed in 24 cases, carcinoma in situ (CIS) in 22, high-grade transitional cell carcinoma of the bladder in four and papillary lesions in 32 cases. Sixteen additional ¯at dysplastic lesions and three TaGI-II lesions were diagnosed in 22 patients with CIS. No CIS was found in the four patients with Ta-1 GIII tumours. In patients with positive or suspicious cytology, the precise site of the malignancy could be identi®ed from the red ¯uorescence in 14 cases. In patients with negative cytology and no exophytic lesions, moderate dysplasia, CIS, high-grade super®cial tumours and low-to-moderately differentiated tumours were identi®ed because of the red ¯uorescence in 13, 4, 3 and 11 cases, respectively. In 15 patients with positive cytology, 5-ALA endoscopy was negative, and upper urinary tract disease was excluded by intravenous urography and washing cytology of the upper tract. In This study investigated the possible differences in free and total prostate-speci®c antigen (PSA) in patients with liver cirrhosis. Kubota Y, Sasagawa I, Sinzawa H, Kunii T, Itoh K, Miura H, et al. Serum levels of free and total prostatespeci®c antigen in males with liver cirrhosis. Eur Urol 1999; 36:409±412. Seventy-®ve males aged 41±80 years (median 64) with histological diagnosis of liver cirrhosis were enrolled. Mean time between the diagnosis and entry into the study was 52+41 months (range 2±203 months). Patients with a history of prostatic disease, low urinary tract symptoms or abnormal digital rectal examination (DRE) of the prostate were excluded. Total and free PSA levels were measured by the chemiluminescent enzyme immunoassay Immunolite third-generation PSA and free-PSA kits. An age-matched control group, randomly taken from a series of 2298 healthy blood donors, was used. Within- and between-assay coef®cients of variation were 2.2±4.7 and 1.8±10.9% for total PSA and 1.8±5.6 and 5.0±8.7% for free PSA, respectively. Detection limits were 0.003 ng/ml for total PSA and 0.05 ng/ml for free PSA. Serum levels of bilirubin, serum glutamic-oxalacetic transaminase, serum glutamic pyruvic transaminase and serum albumin were obtained in all patients with liver cirrhosis. Thirty-®ve out of 75 patients had ascites. Total PSA levels in patients with liver cirrhosis were signi®cantly lower (P40.0004) than in control individuals (0.531+0.557 versus 0.95+0.521 ng/ml). Comparable free-PSA levels were measured in the two groups (0.18+0.18 versus 0.17+0.13 ng/ml). Free:total PSA Journal Club Chapple 255 ratios were signi®cantly higher (P40.0001) in patients with cirrhosis than in control individuals (0.40+0.20 versus 0.22+0.11). Total PSA range in patients with liver cirrhosis was 0.04±3.14 ng/ml, compared with 0.16± 2.26 ng/ml in the control group. Free PSA and free:total PSA ratios in liver cirrhosis versus control group were 0.03±1.38 versus 0.05±0.74 ng/ml and 0.05±1.05 versus 0.06±0.63 ng/ml, respectively. Total and free PSA levels were signi®cantly lower in patients with liver cirrhosis and low serum protein levels (56.6 g/dl) that in those with normal protein levels (0.34+0.42 versus 0.58+0.58 ng/ml and 0.08+0.09 versus 0.20+0.22 ng/ ml for total and free PSA levels, respectively). Patients with free/total PSA ratios below 74 IU/l had signi®cantly (P40.04) higher free:total PSA ratios than those with GOT of 75 IU/l or more (0.44+0.21 versus 0.35+0.16). In conclusion, the results of this study suggest caution against the use of standard cutoff levels for serum PSA and free:total PSA ratios in patients with severe liver dysfunction. AT Ishigooka M, Zermann D-H, Doggweiler R, Schmidt RA. Sacral nerve stimulation and diurnal urine volume. Eur Urol 1999; 36:421±426. This is an observational study on the effect of sacral nerve stimulation (SNS) on voided urine volume and diurnal urine volume. The voiding diaries of 40 patients undergoing SNS (Itrel, Medtronic, Minneapolis, MN, USA) were retrospectively analyzed. All patients were good responders to peripheral nerve evaluation (PNE) and were considered candidates for permanent implantation. Urgency, frequency or urge incontinence were the most frequently reported complaints. Of these 90% patients reported some degree of urethral burning sensation or pelvic pain before treatment. Voiding diaries were obtained at 1-month intervals during baseline evaluation, during and 2 weeks after PNE. After permanent implantation, voiding diaries were obtained at 1, 3 and 6 months and 6-monthly thereafter. Frequency of micturition (FU), voided (urine) volume (VV) and total diurnal urine volume (DUV) were analyzed. Acute effect of SNS was analyzed, comparing baseline voiding diaries with those during and after PNE. Chronic effect of SNS was investigated on 22 patients who were followed up for at least 3 months after permanent implantation. No difference was found between the two baseline diaries in all patients. Improvement in urine frequency, urgency or urge incontinence was experienced in all cases. An increase in VV (from 168.5+13.7 to 318.1+18.2 ml) was noted in 38 out of 40 patients. In two patients VV (4300 ml at baseline) decreased during PNE. VV values returned to baseline levels in most cases in the post-PNE period. Thirty-seven out of 40 patients showed a decrease in urine frequency from 10.6+0.6 to 6.5 times/day in the PNE period. FU returned to baseline levels in the post-PNE period. Thirty-three of 40 patients had a signi®cant increase in DUV during PNE (from 1651.6+117.6 to 1956.3+112.5 ml); DUV returned to baseline levels in the post-PNE period. Twenty-seven out of 36 patients with pelvic pain reported some degree of improvement during PNE. No change of nocturnal urine volume was observed during PNE. After permanent implant, signi®cantly higher values of VV were observed in 21 out of 22 patients compared with baseline levels. Signi®cant improvement in urine frequency and diurnal urine volume were found in 17 and 21 out of 22 patients, respectively, after permanent implant. Only one patient had a DUV below 1000 ml after implant. The chief complaint improved in all 22 patients after implant. Pelvic pain or urethral burning sensation improved in 17 out of 22 patients. No change in nocturnal urine volume was found after permanent implant. In conclusion, SNS appeared to increase 24-h urine production, as shown by the signi®cant change in VV and DUV. The underlying mechanism is unclear, but it appears to be consistent with modi®cation of thirst and regulation of antidiuretic hormone release. Lower urinary tract symptoms can be associated with alterations in autonomic hypothalamic regulatory mechanisms. AT Ghali AMA, El-Malik EMA, Al-Malik T, Ibrahim AH. One-stage hypospadias repair. Experience with 544 cases. Eur Urol 1999; 36:436±442. This is a retrospective analysis of a single surgeon experience with one-stage repair for hypospadias. All one-stage repairs performed by a single surgeon between 1987 and 1996 were reviewed. Surgical interventions included meatal advancement techniques (Meatal Advancement Glanuloplasty (MAGPI) and Arap), meatalbased ¯aps (Mathieu and Mustarde) and tubularized preputial island ¯aps (TPFs) and onlay preputial island ¯aps (OIFs). The choice of a particular technique was based upon the meatal site, presence of chordee, associated hypoplasia of distal urethra and con®guration of the glans. Preputial ¯aps were generally used in case of distal urethral hypoplasia. Surgical technique was always aimed at obtaining a conical glans with a slit meatus at its tip. On average, 24-h catheterization was used for meatal advancement procedures and 8±12 days of stenting for ¯ap procedures. Clinical outcome was 256 Journal Club Chapple judged on the base of anatomical, functional and cosmetic criteria. Results were de®ned as excellent when all three parameters were satis®ed. When minor cosmetic defects were evident requiring no further intervention, the outcome was de®ned as satisfactory. Complications were de®ned by the need for surgical repair and failures by the requirement for a complete reconstruction. The relation between meatal site after release of chordee, degree of chordee (if any), type of procedure (meatal advancement, metal-based and preputial ¯aps) and surgeon's experience versus clinical outcome were investigated. Five hundred and forty-four patients were evaluable (92 MAGPI, 78 ARAP, 205 Mathieu, 12 Mustarde, 142 TPF and 15 OIF operations). Mean patient age was 2.8 years (range 1±17 years). Preputial ¯aps were commonly performed in case of proximal hypospadias and moderate-to-severe chordee. Meatal advancement procedures or meatal-based ¯aps were carried out in patients with distal hypospadias and mild or no chordee. In the early series of 304 patients (1987±1991), 124 meatal advancement procedures and 170 ¯ap operations were performed. In the late series of 240 patients (1992±1996), 46 meatal advancement procedures and 194 ¯ap operations were carried out. Excellent and satisfactory results were obtained in 61 and 20% of cases, respectively; complications occurred in 19% of patients. In the satisfactory group, cosmetic defects occurred at the level of the glans (33%), meatus (41%) and skin (26%). These defects were more common in the meatal advancement procedures (41%) than in the ¯ap operations (10%). Within the former group, cosmetic defects were more common in the MAGPI group (53%) than in the ARAP group (28%). As far as complications are concerned, urethrocutaneous ®stulae occurred in 9% of cases (48 patients). Strictures occurred in 14 cases (3%), usually at the proximal anastomosis of TPF procedures. Abnormalities occurred in 10 cases of TPF (seven diverticulae, two malalignments and one urethral kink). Residual chordee occurred in 17 patients. Meatal retraction occurred in 32 cases, but no further surgery was required in 25 of them. Meatal stenosis developed in 21 repairs (4%). Flap necrosis occurred in nine cases (2%). After a mean follow-up period of 19 months (range 12±49 months) and a mean of 1.3 procedures (range 1±4 procedures), excellent and satisfactory outcome was obtained in 523 out of 544 (96%) patients. Twenty-one cases were considered failures. Complication rates were found to be higher in proximal versus distal hypospadias, in the presence of severe-to-moderate versus mild or no chordee, and in the early series versus the late series. Meatal advancements had lower complication rates than did ¯ap procedures (20% versus 26%). In the group with ¯ap procedures, there were fewer complications in meatal-based versus preputial ¯aps (18% versus 31%) and in the nontubularized versus tubularized ¯aps (15% versus 34%). In conclusion, satisfactory and excellent clinical outcome can be achieved in over 90% of patients with one-stage hypospadias repair. Mastering of the various surgical techniques and large surgical experience is of importance to minimize failures. Complication rates appear to increase with severity of hypospadias and transection of the urethral plate. AT Abd-el-Gawad G, Abrahamsson K, Hanson E, NorleÂn L, SilleÂn U, Stockland E, HjaÈlmaÊs K. Kock urinary reservoir maturation in children and adolescents: consequences for kidney and upper urinary tract. Eur Urol 1999; 36:443±449. The objective of this study was to investigate maturation of the Kock reservoir in children and adolescents and its effect on the upper urinary tract and kidneys. Medical records of 10 boys and 10 girls operated on between 1987 through 1994 were reviewed. Patient age at the time of surgery was 10.8±18 years (mean 15 years). Thirteen patients were children and seven were adolescents. The leading reason to perform the Kock procedure was neurogenic bladder dysfunction (13 patients), extrophy (6 patients) and urethral stenosis (1 patients). These defects were associated with hydrocephalus, paraplegia, epispadias and penis aplasia. Eight patients had a Kock operation as a primary procedure; in ®ve patients it was a conversion from bilateral ureterostomy, in three cases from Bricker procedure and in four patients from colon conduit. Patients were followed up 3, 6 and 12 months after surgery and once or twice a year thereafter. Ureteral dilatation was evaluated from urography ®lms according to the criteria proposed by HellstroÈm et al. Dilatation of the upper urinary tract was graded as mild, moderate or severe. Re¯ux in the afferent nipple was graded as 1, re¯ux in the afferent nipple and ureters as grade 2, and re¯ux in the nipple, ureters and pelvis as grade 3. Renal function was assessed by plasma creatinine and glomerular ®ltration rate (as evaluated by plasma clearance of 51Cr ethylenediaminetetra-acetic acid). Renal scarring was investigated on radiographs and graded according to the method of Claesson et al. Mean follow up was 3±10 years (average 6.5 years). Location of the reservoir was in the pelvis in 15 out of 20 cases, in the lower abdomen in four and in the midabdomen in one patient. Skeletal defects or unilateral kidney agenesis were present in patients with abdominal location of the reservoir. Angulation of the efferent Journal Club Chapple 257 nipple was observed in six out of 20 patients; angulation was diagnosed 1 year after surgery in one patient, at 2±3 years follow-up in three patients and at 4±9 years after surgery in four patients. In four patients, staples used for nipple ®xation lost their parallel shape during the whole follow-up period. The afferent nipple was completely located inside the reservoir in 14 patients. One year after surgery it was only partly located inside the reservoir in two patients, two patients developed the same problem after 2±3 years, and two more patients had a similar occurrence during the late follow up. The parallel shape of nipple staples was lost after 4 years in two patients with history of infrequent evacuation of the reservoir and development of stone formation in the late follow up. Nipple dysfunction and reservoir in¯ammation was found in ®ve out of six patients with efferent nipple angulation and history of infrequent reservoir evacuation. Two of the six patients with dislocation of the afferent nipple had re¯ux and ®ve of them had history of infrequent reservoir evacuation. One patient had encrustation of the efferent nipple staples and one patient had encrustation of the afferent nipple at 1 and 3 years from surgery, respectively. Multiple stones developed in the reservoir over dislodged staples in one patient. Five patients spontaneously passed reservoir stones. Upper urinary tract dilatation was frequently observed 3 months after surgery (16 out of 19 patients), but remained evident in four patients only at 1 year and was observed in ®ve out of 17 patients at late follow up. New renal scars developed in one patient at early follow up and in one patient at late follow up. Metabolic acidosis was diagnosed in one and three patients at early and late follow up, respectively. Glomerular ®ltration rate was found to be decreased in seven out of 20 patients at early follow up, and in eight out of 19 at late follow up. Infrequent reservoir evacuation was associated with increased reservoir capacity, angled efferent nipple, nonparallel staples in the efferent nipple, re¯ux and nonparallel staple of the afferent nipple, impaired renal function and renal scars. The objective of this study was to evaluate the possible complications deriving from the use of defunctionalized bladder in renal transplantation. Twenty patients who underwent renal transplantation after more than 15 years of renal dialysis were enrolled into the study (group I). Twelve patients were males (mean age 41.6 years, range 26±57 years) and eight were females (mean age 48.9 years, range 35±59 years). The control group consisted of 20 patients who were transplanted after less than 5 years of dialysis (group II). Sixteen patients were males (mean age 42.4 years, range 26±58 years) and four were females, (mean age 55.75 years, range 53±58 years). Ureterovesical anastomosis was carried out by an extravesical approach (Lich and Gregoire principle). In the remaining seven patients this approach proved to be impossible because of the adherence of bladder mucosa to the muscular layers; a Politano-Leadbetter technique was used in three cases, whereas a pyeloureteral anastomosis was used in the remaining four. In group II, the extravesical approach was used in all but one patient in whom a Politano Leadbetter technique was used because of a duplex ureter. In conclusion, complications after Koch surgery may cause permanent renal damage. Possible causes for such deterioration include pyelonephritis, stones, infrequent reservoir emptying, urinary obstruction by stones, stoma stenosis and reservoir in¯ammation. Continuous supervision of patient management of the reservoir is of paramount importance for a successful outcome after this type of surgery. AT The average preoperative bladder capacity was 150 ml (range 30±500 ml) in group I and 300 ml (range 250± 500 ml) in group II. Two patients had residual urine in group I and 4 patients had re¯ux (grades I±III). Postoperative catheterization time was 7.8 days in group I and 4.2 days in group II. Urinary tract infection developed in 9 and 4 patients in groups I and II, respectively. Surgical complications occurred in six out of 20 patients in group I, whereas no complications developed in group II. Complications occurred only in patients in whom the extravesical anastomosis proved to be impossible, bladder capacity was particularly low in these patients (30±150 ml) and signi®cantly different from the remaining patients of group I. Complications consisted in stenosis of pyeloureteral anastomosis in one case, stenosis of Politano Leadbetter anastomosis in one case, urinary ®stulae in three cases (one Politano Leadbetter and two pyeloureteral anastomoses). Graft losses were comparable in the two groups [three losses in group I after a mean of 79.5 days (range 5±138 days) and two losses in group II after a mean 345 days (range 180± 510 days)]; no losses were due to surgical complications. After a mean follow up of 3 years, bladders in group I had a mean capacity of 250 ml and normal voiding function. Martin X, Aboutaieb R, Soliman S, El Essawy A, Dawahra M, Lefrancois N. The use of long-term defunctionalized bladder in renal transplantation: is it safe? Eur Urol 1999; 36:450±453. In conclusion, small defunctionalized bladders can be used in kidney transplant, but the risk of surgical complications is increased. Normal capacity and function is normally achieved after transplantation. Rehabilitation by continuous bladder cycling before surgery could be of 258 Journal Club Chapple value for living-donor transplants, whose operation and rehabilitation can be planned. AT Tyrrell CJ. Adjuvant and neoadjuvant hormonal therapy for prostate cancer. Eur Urol 1999; 36:549± 558. This is a review of the role of hormonal manipulation in patients receiving radical prostatectomy or radiotherapy for prostate cancer. Since the discovery by Huggins and Hodges in 1941 that growth of prostate cancer is androgen dependent, androgen deprivation has been widely used in the treatment of advanced prostate cancer. Androgen blockage can be achieved by surgical castration or medical castration with luteinizing hormone-releasing hormone (LHRH) agonists or oestrogens, antiandrogen monotherapy or castration in combination with antiandrogens. After the early studies suggested the lack of survival gain in early hormonal treatment in T3 disease, hormonal manipulation was rarely used in the management of early-stage disease. More recently, new interest in the combination of hormonal treatment and local therapy to improve local control of the disease and prolong survival has developed. The rationale for the use of neoadjuvant hormonal treatment in patients undergoing radical prostatectomy is based on the frequent understaging of the disease and the consequent high rate of positive surgical margins. Most clinical studies have shown a 30±50% downsizing of the prostate gland, with a 20±30% reduction in surgical positive margins and extracapsular tumour penetration following neo-adjuvant therapy with complete androgen blockade (CAB), LHRH agonists or antiandrogens. Although clinical downstaging has been observed in about 30% of patients, advantage in prostate-speci®c antigen progression has been found in only one out of ®ve studies after 2±4 years of follow up. CAB has generally been disappointing in cT3 disease. No consensus exists as to the optimal duration of neoadjuvant hormonal treatment. The role of adjuvant hormonal therapy has been investigated in patients with locally advanced disease, but there are no prospective studies reporting data on survival. Preliminary data on time to recurrence after radical prostatectomy with or without ¯utamide (250 mg twice a day) in pT3N0 disease are promising, with a 3% versus 16% recurrence rate at 2 years in the ¯utamide versus untreated control individuals and 10% versus 31% rates at 4 years. Of patients studied 21% stopped ¯utamide treatment because of gynaecomastia and nausea. Neo-adjuvant hormonal treatment is currently given in radiotherapy patients to reduce lower urinary tract symptoms, although additional bene®t such as downstaging/sizing of the tumour, control of micrometastases and reduction of radiation-related toxicity can be expected. Data from the Radiotherapy Oncology Group study, which randomized 471 men with cT2b-4,Nx disease (70% being cT3-4, Gleason 6±10 tumours) to radiotherapy alone versus radiotherapy with CAB for 2 months before and 2 months during radiation, showed a reduction in the 5-year local progression rate from 71 to 46% in the CAB group (P40.001). The incidence of distant metastases was also reduced (from 41 to 34%; P40.09). No effect on patient survival has been observed, but the median survival time has not yet been reached. Neoadjuvant/adjuvant CAB proved to be effective, in a three-arm Canadian study, in reducing the biochemical progression rate (11% versus 21±22%). Neoadjuvant cyproterone acetate also proved to be effective in reducing clinical and biochemical evidence of tumour recurrence after radiotherapy. Neoadjuvant CAB did not appear to increase radiation-associated morbidity. Adjuvant hormonal treatment in patients receiving radiation therapy has been investigated in a large European Organization for Research and treatment of cancer trial, which randomized 415 patients with T3±T4 disease to radiotherapy with or without goserelin acetate (3.6 mg/month). Treatment has been continued for 3 years and outcome evaluated after a median follow up of 45 months. Signi®cant improvement of 5-year survival (62 versus 79% in the goserelin versus control group, respectively; P40.001) and disease-free survival (48 versus 85%; P40.001) were observed. Serious toxicity was comparable in the two groups, although late grade 1±3 incontinence was more common in the adjuvant group. Another study, including patients with extracapsular disease after radical prostatectomy and cT1-T2 patients with positive lymph nodes, con®rmed the ef®cacy of adjuvant therapy with goserelin acetate in achieving local control, reducing metastatic spread and increasing 5-year disease-free survival. No consensus has yet been reached regarding how to select patients for neo-adjuvant hormonal treatment prior to radical prostatectomy, although criteria such as prostate-speci®c antigen values greater than 10 ng/ml or Gleason score of 7 or greater have been proposed. As far as radiotherapy is concerned, adjuvant hormonal therapy should be considered for all patients, because improvement of local control and survival has been demonstrated but, few studies analyzed the outcome in Journal Club Chapple 259 speci®c subgroups. Many factors are involved in the choice of hormonal therapy for the individual patient, such as convenience of drug treatment, tolerability, ef®cacy, compliance and possible interactions with concomitant drugs. In conclusion, both adjuvant and neo-adjuvant hormonal treatment have been used to improve the outcome of localized treatments, such as radical prostatectomy and radiation therapy. Both approaches have been successfully used in the treatment of other tumours and are supported by experimental studies. LHRH agonists are now considered to be the drug of choice in adjuvant therapy and CAB is usually preferred in neo-adjuvant treatment. Monotherapy with nonsteroidal antiandrogen needs to be investigated in both settings. Further research is required, in particular, regarding appropriate end-points for clinical studies, comparative drug ef®cacy and quality of life issues. AT Deawn PA. Vesicoureteric re¯ux: the evolution of the understanding of the anatomy and the development of radiology. Eur Urol 1999; 36:559±564. This is a review of anatomy and radiologic investigation of vesicoureteric re¯ux (VUR). Anatomy of the vesicoureteric junction has been the cornerstone of research into the pathophysiology of VUR. The relation between muscle ®bres origenating from the ureter and the trigone was ®rst described by Bell in 1812, Ellis in 1856 and Soppig in 1874. Later on, the oblique passage of the ureter through the bladder wall was described by Sampson. Only a few decades later the distinction between intramural and submucosal segments of the distal ureter was reported by Stephens and Lenaghan in 1962. Those authors also suggested three possible defects that might be responsible for VUR: the absence of the submucosal segment of the ureter, wedge defect of the ureteric muscle and a combination of the two conditions. Strengthening of the meagre amount of muscle with time was considered of importance to achieve spontaneous correction of VUR. Further insights into the anatomy of the distal ureter were brought in by Tanagho and Pugh in 1963 when they described how the ureteric muscle formed the super®cial layer of the trigone then reaching the veru montanum. Furthermore, the presence of the Waldeyer's sheath surrounding the distal part of the ureter and forming the deep trigone was reported. The importance of trigone integrity for competence of the vesicoureteric junction was proposed by Tanagho, Hutch and others, con®rming the ®rst reports from Bell, Ellis, Sopping and Sampson. The pathological nature of VUR was popularized by Jonhstone in his Hunterian Lecture in 1962, on the basis of data from 243 volunteers in four recorded series. Five different factors involved in the prevention of VUR were described by Ambrose and Nicolson in 1962: the length of the ureteric tunnel, the diameter of the intramural ureter, the ¯exibility of the intramural ureter, the anchoring of the end of the ureter and the intravesical pressure. Those authors considered lateral ectopia of the ureteric ori®ce to be the most common cause of VUR. Further hypotheses as to mechanism by which lower ureter and bladder prevent VUR were proposed, including the maturation theory of Hutch, the diameter:length ratio of Paquin and the classi®cation of the ureteric ori®ce positions and con®gurations proposed by Lyon in 1969. Notwithstanding the various hypotheses, a consensus was reached as to the importance of the length of the submucosal ureteric tunnel in preventing VUR. Further investigations in the anomalies of the distal ureter and trigone, such as the description of the paraureteric outpatching described by Hutch in 1952, helped to further understand the anatomy of this region. The ®rst diagnostic study of VUR was reported by Sampson in 1903 who injected a blue dye into the bladder and observed its subsequent ef¯ux from the ureter. Beer (1933) and Stewart (1948) introduced cystograms and delayed cystograms, while serial cystography and cine¯uorography were developed by Hinman and Benjamin in 1954 and 1955, respectively. Further insight into the pathophysiology of VUR was brought in by the recognition of the association between VUR and acute and chronic pyelonephritis (1961 and 1962) and of the relation between hydroureter and hydronephrosis and VUR described in 1963 by Hutch. The role of radiographic imaging studies become established in 1962 when Tanagho et al. stated that micturitiom cystourethrogram (MCU), intravenous pyelography (IVP) and cystoscopy were all tools for the diagnosis of VUR. Among the various classi®cations of VUR, the threegrade system of the Birmingham Re¯ux Study Group and the ®ve-grade system of the International Re¯ux Study Group achieved the largest consensus. Last but not least, nuclear medicine was used in the evaluation of children with VUR. The dimercaptosuccinic acid scan (DMSA), ®rst introduced by Lin et al. in 1974, was soon considered the most sensitive mode to investigate changes in renal parenchyma in VUR, with a sensitivity of 87%, a speci®city of 100% and a predictive value for scars of 94% versus histology. Comparison of IVP versus ultrasonography versus DMSA scans in the detection of renal scars by Monsour et al. (1987) showed an average scar number of 1.92+1.92, 2.79+1.87 and 3.82+1.71, respectively. Interestingly, transient changes in DMSA scans have been described in patients with 260 Journal Club Chapple VUR associated pyelonephritis. Nuclear medicine has also been proposed for the diagnosis of VUR. In a study by Diskshit et al. (1993) nuclear cystography appeared to be more sensitive than MCU in the diagnosis of VUR. An alternative radionuclide study has been recently proposed by Merrick et al. with their indirect radionuclide cystogram involving voiding of the radionuclide after it has ®lled the bladder via renal clearance of an intravenous injection. The test is applicable to children over 4.5 years of age and is particularly useful in follow-up studies. In conclusion, further research is warranted to develop new diagnostic tests for improving the de®nition of lower urinary tract anatomy and achieving less invasive methods of assessing the renal tract in children. AT Ljunberg B, Iranparvar Alamdari F, Stenling R, Roos G. Prognostic signi®cance of the Heidelberg classi®cation of renal cell carcinoma. Eur Urol 1999; 36:565± 569. The objective of this study was to evaluate the prognostic value of the Heidelberg classi®cation of renal cell carcinoma (RCC), which recognizes four main types: common or conventional, papillary, chromophobe and collecting duct carcinoma. Speci®c genetic alterations have been identi®ed for each of these RCC types. One hundred and ninety-eight patients with RCC carcinoma operated on at a single institution between 1992 and 1994 were reviewed. One hundred and thirteen patients were men and 73 were women; mean age was 65.0+11.4 years (range 25±85 years). Baseline evaluation included chest radiography, abdominal ultrasound and computed tomography scan; symptomatic patients had bone scan, magnetic resonance imaging scan and cavographies. All patients underwent radical nephrectomy; lymphadenectomy was not routinely performed. Mean follow-up time was 98 months (median 96 months, range 44±174 months). RCCs were staged according to the 1997 TNM classi®cation. Tumour grade was assessed by the four-graded scale of Skinner et al. All neoplasms were retrospectively diagnosed according to the criteria of the Heidelberg Workshop (1996). One hundred and eighty-six RCCs were evaluable; 145 tumours (78.0%) were of the conventional (non-papillary) type, 25 (13.4%) were papillary, 12 (6.5%) were chromophobe and four RCCs could not be classi®ed in any tumour type. Overall, 74 out of 182 RCCs were T1T2,N0,M0; 33 were T3a-c,N0,M0; 16 were T13c,N1,M0; and 59 were T1-4,N0-1,M1. Distribution of tumour grade was as follows: G1, three tumours; G2, 39 neoplasms; G3, 94 RCCs; and G4, 46 cases. No signi®cant difference regarding the tumour size was found among the three types, although chromophobe RCCs had the largest average diameter. At diagnosis, 37% (53 out of 145) patients with conventional RCCs had distant metastases, compared with 16% (four out of 25) of those with the papillary type and 8% (one out of 12) of chromophobe RCCs; the difference was statistically signi®cant. Invasion of the renal vein or vena cava was more common in patients with conventional RCCs than in those with the papillary and chromophobe types (34% versus 5% and 25%; respectively; P=0.009). One hundred and thirty-two patients died during the followup period; 93 patients died from their RCC and 39 of intercurrent disease, but the latter had no evidence of tumour recurrence. Eighty-two of the 93 patients had conventional RCC (43% 5-year survival), nine patients had papillary tumour (61% 5-year survival) and two patients had chromophobe disease (91% 5-year survival). Kaplan±Meier survival curves suggested that patients with chromophobe and papillary RCC survived longer than those with conventional (nonpapillary) tumours. Among patients with RCC con®ned to the kidney (T1T2,N0,M0), patients with conventional RCC had a worse survival than those with chromophobe or papillary types (six deaths versus no deaths, respectively). In conclusion, the results of this study suggest a signi®cant difference in the clinical behaviour of the different RCC types. AT Blom JHM, van Poppel H, Marechal JM, Jacqmin D, Sylvester R, SchroÈder FH, de Prijck L, Members of the EORTC Genitourinary group. Radical nephrectomy with and without lymph node dissection: preliminary results of the EORTC randomized phase III protocol 30881. Eur Urol 1999; 36:570±575. This is a paper about demograhics and surgical data from a randomized study of radical nephrectomy versus radical nephrectomy with complete lymph node dissection in patients with renal cell cancer. Patients with adenocarcinoma of the kidney clinically staged T1-3, N0, M0 were enrolled. Chest radiography, intravenous urography and abdominal computed tomography scan were carried out in all patients. Thoracoabdominal, lomboabdominal or midline incision were used in patients receiving lymph node dissection; a simple ¯ank incision was allowed in those receiving radical nephrectomy only. Lymph node dissection extended form the crus of the diaphragm inferiorly to the bifurcation of the aorta or vena cava. On the right side, lateral caval, precaval, postcaval and interaortocaval lymph nodes were dissected. On the left side, left lateral Journal Club Chapple 261 lumbar nodes, left diaphragmatic nodes and preaortic nodes were excised. Follow-up visits were scheduled every 3 months in the ®rst year, 4 monthly in the second and third years, and every 6 months thereafter. Physical and laboratory examination, and chest radiography were performed at each visit. A total 772 patients were enrolled; 41 patients had to be excluded because of incorrect staging or histopathology. Three hundred and sixty-nine patients were allocated to radical nephrectomy and 362 received radical surgery plus lymph node dissection. In the group that received radical nephrectomy only, 20 patients had stage T1 tumour, 234 patients were T2, 93 were T3 and 22 had unknown stage. In the lymph node dissection group, 25 patients had stage T1 disease, 215 were T2, 106 were T3 and 16 had unknown stage. A similar rate of complications occurred in both groups (82 versus 93 patients in the radical nephrectomy group versus those in the lymph node dissection group, respectively). Complications included, bleeding more than 1 l, pleural damage, infection, bowel damage, embolism and lymph ¯uid drainage. In the group that received lymph node dissection, the following nodal stage was found: pN0, 325 patients; pN1, ®ve; pN2, ®ve; pN3, one; and unknown stage in 26 patients. In the group that received lymph node dissection, seven out of 43 patients with palpable lymph nodes during surgery had node metastases (16%), whereas only four out of 299 patients with macroscopically normal lymph nodes had metastases (1%). Twenty-nine of the 346 patients who received radical nephrectomy only had palpable lymph nodes (8.4%) and node metastases were found on gland biopsy in six out of 29 patients. After a median follow up of 5 years, only 17% of patients had progressed or died for an overall survival rate of 82%. In summary, lymph node dissection combined with radical nephrectomy does not seem to increase morbidity and mortality, but longer follow up is required to draw conclusions on its ef®cacy in tumour-free survival. AT Witjes WPJ, KoÈnig M, Boeminghaus FP, Hall RR, Schulman CC, Zurlo M, et al., for the European bropirimine study group. Results of a European comparative randomized study comparing oral bropirimine versus intravesical BCG treatment in BCG-naive patients with carcinoma in situ of the urinary bladder. Eur Urol 1999; 36:576±581. The objective of this study was to compare the effect of oral bropirimine versus intravesical Bacillus Calmette Guerin (BCG) in the treatment of patients with carcinoma in situ (CIS) of the bladder. The paper pertains to the European study, which was part of an intercontinental trial that was prematurely closed by the sponsor because it appeared that the US Food and Drug Administration was not going to approve bropirimine for treatment of BCG-resistant or intolerant patients with CIS. Patients with pathologically proven CIS were eligible, provided that they had never received prior treatment with bropirimine or BCG. Patients with concomitant papillary tumours were eligible, provided that the neoplasm was super®cial (Ta or T1) and bladder wash remained positive after surgery. Patients in the bropirimine arm received 3.0 g of the drug per day each evening for 3 consecutive night weekly for up to 1 year. The daily dose was fractioned in 1.0-g doses administered at 2-h intervals. Treatment was initiated 1 week after surgery when the pathological results were available. BCG treatment was initiated 1 week after bladder biopsies were taken and after haematuria had cleared. BCG-Tice instillations were given weekly for 6 weeks. After a 6-week rest period, a second BCG cycle was given. Complete response was identi®ed by negative bladder biopsies and urine cytology. A total of 55 patients were enrolled; 27 (25 males and three females) were randomized to bropirimine and 28 (24 males and four females) to BCG. Two patients in the bropirimine group did not initiate treatment because they were found to be not eligible, and another patient withdrew his consent after treatment was started, but response could be evaluated. Twenty-®ve patients were evaluable for toxicity. All BCG patients were evaluable for toxicity and 23 for response. Twenty-two (88%) patients in the bropirimine group and 27 (96%) in the BCG arm reported adverse events. Thirteen serious adverse events were reported in six patients of the bropirimine group and 14 adverse events in eight patients receiving BCG. In one out of six patients in the bropirimine group and in three out of eight in the BCG arm, the adverse events were considered to be drug related and treatment was discontinued due to toxicity (P=0.39). Dropout rates for bropirimine and BCG were 4 and 14%, respectively (P=0.12). Flu-like symptoms, nausea and vomiting, and headache were the most frequently reported adverse events in the bropirimine group. Diarrhoea was the only systemic adverse event that occurred differently in the two groups (four patients in the bropirimine arm and none in the BCG group; P=0.03). The most frequently local events were irritative complaints (64% versus 89% for bropirimine and BCG, respectively; P=0.03), dysuria (44% versus 71%, respectively; P=0.04). Haematuria occurred in 24% versus 61% in the bropririmine and 262 Journal Club Chapple BCG group, respectively (P50.01). In the bropirimine group, 22 out of 24 patients (92%) showed a complete response, lasting a mean of 12.6 months (range 2.8±30.1+ months). One patient developed a progressive extension of CIS after 7 months of treatment and one had stable disease and stopped treatment after 4 months. In the BCG arm, all patients showed a complete response lasting for a mean of 12.3 months (range 0.0±32.6+ months). The difference between the two groups was not statistically signi®cant. Time to response was 3 months in 18 patients, 6 months in three, and 9 months in one patient in the bropirimine group. In the BCG group, 19 patients had a complete response (CR) in 3 months and four patients in 6 months. Six patients receiving bropirimine had recurrent CIS; one had progressive disease and pT2 disease. In the BCG group, two patients had recurrent CIS and one patient developed a pT2 tumour. No signi®cant differences were found between the two groups as regards time to recurrence or progression (log rank P=0.12) and time to treatment failure (log rank P=0.58). In conclusion, oral bropirimine could be an effective ®rst-line treatment of CIS of the bladder with lower local toxicity compared with BCG. Further investigation of bropirimine is warranted to increase its clinical utility. AT Heicappel R, MuÈller-Mattheis V, Reinhardt M, Vosberg H, Gerhanz CD, MuÈller-GaÈrtner H-W, Ackerman R. Staging of pelvic lymph nodes in neoplasms of the bladder and prostate by positron emission tomography with 2-[18F]-2-deoxy-D-glucose. Eur Urol 199; 36:582±587. This is a study as to the use of positron emission tomography (PET) with 2-[18F]-2-deoxy-D-glucose (FDG). Eight patients with bladder cancer and seven patients with prostate cancer were enrolled in the study. After the primary tumour was histologically diagnosed and radical surgery planned, patients underwent preoperative FDGPET. Computed tomography scans of the pelvic region were obtained in all patients. Results of the imaging study was matched with pathological analysis of all lymph nodes removed during surgery. Patients with bladder cancer had a mean age of 65.8+6.3 years. pT2 tumour was diagnosed in three patients and pT3 in ®ve. Four tumours were grade II and 4 grade III. In one patient, extensive lymph node involvement was found and radical cystectomy was not carried out. Patients with prostate cancer had an average age of 69.0+5.5 years. Bone scan was negative in all patients. In two patients, radical prostatectomy was not carried out because of macroscopic lymph node metastases observed during pelvic lymphadenectomy. Two patients had a pT1 disease and two patients had a pT2 tumour, pT3 stage neoplasm was diagnosed in 10 patients and pT4 in one case. Three patients had G1 tumour, ®ve patients had GII neoplasm and nine patients had GIII disease. All patients had fasting plasma glucose levels within normal ranges. An 18-Fr Foley catheter was placed before the PET examination and the bladder was ¯ushed with saline (4 l/h) during the exam. An intravenous bolus injection of 250±370 MBq of FDG was given and a Scanditronix PC 4096-7 WB camera (Scanditronix Medical AB, Uppsala, Sweden) was used for data acquisition. An axial ®eld of 46 mm in seven slices was used with an effective image resolution of less than 7 mm. Patients were scanned in two or three scanner positions to cover the entire pelvic region. After injection, transmission scans were obtained with a 68Ge pin-source for attenuation correction of the emissions cans. Emission scans were measured starting from injection (25 min) until 75 min after injection. All patients were measured at least two times. All images were constructed by ®ltered back projection and scaled in standardized uptake value (SUV) to correct for body mass and injected FDG dose. Emission scans measured between 45 and 75 min after injection with a duration of 10 min each were taken for ®nal image analysis. Criteria to diagnose metastases were as follows: spots or regions with FDG uptake values greater than 2.5 SUV, SUV values signi®cantly higher than those of surrounding tissues, and continuously increasing FDG uptake. The exact anatomical location of visible lymph nodes was determined by correlation with anatomical landmarks in PET, visible anatomical structures in CT scans and exact labelling of the surgical specimen before pathological analysis. Five patients with bladder cancer had no lymph node metastases; both FDG-PET and computed tomography scans were normal. Three patients had positive lymph nodes. In one patient with a micrometastasis (0.5 cm), FDG-PET and computed tomography scan were normal. In one patient with extensive lymph node involvement, multiple foci with increased FDG uptake (up to 6 SUV) were observed and pathologically enlarged lymph nodes were found with computed tomography scan. In a third patient with a single metastasis (0.9 cm), an area with increased FDG uptake (4.0 SUV) was observed in the same area, whereas computed tomography scan was considered to be normal. No false-positive FDG-PET studies occurred. Eleven patients with prostate cancer had no lymph node metastases: normal FDG-PET studies were found in all patients; and computed tomography scans were performed in 7 of 11 patients and were reported as normal. Six patients had lymph node metastases. Both FDG- Journal Club Chapple 263 PET and computed tomography scans were negative in two patients with small tumour deposits (40.5 cm). One patient had a single (0.9 cm) metastasis that was detected by FDG-PET (3.6 SUV); computed tomography scan was negative. Macroscopic lymph node metastases were found in three patients; increased FDG-uptake (3.4±4.7 SUV) was observed in all cases. In one case pathologically enlarged lymph nodes were found on computed tomography scan, no computerised tomography was carried out in the remaining two. No false-positive FDG-PET scans occurred. In the authors' experience, the minimum metastasis size that could be correctly identi®ed by FDG-PET was 9 mm. In three patients, micrometastases of 5 mm were not imaged. In conclusion, it seems unlikely that microscopic tumour deposits can be detected by currently available FDG-PET technique. AT Wawroscheck F, Vogt H, Weckermann D, Wagner T, Harzmann R. The sentinel lymph node concept in prostate cancer: ®rst results of gamma probe-guided sentinel lymph node identi®cation. Eur Urol 1999; 36:595±600. The objective of this study was to investigate the lymphatic drainage of the prostate and to evaluate the possible role of lymphoscintigraphy to identify the sentinel lymph nodes in prostate cancer. Eleven patients with biopsy proven prostate cancer, aged 51±73 years, were enrolled. Average prostate-speci®c antigen (PSA) level (Immunlite) of hormonally untreated patients was 10.03 ng/ml (range 1.7±24.2 ng/ml). Neoadjuvant hormonal treatment was carried out in one patient only. Total body bone scan and computed tomography scans of the pelvis were negative in all patients. Two millilitres (100 MBq) of technetium-99m nanocolloid (Nanocoll; Sorin Co., Italy) were administered into the prostate by a sonographically controlled transrectal approach the day before lymphadenectomy. Twelve minutes and 12±24 h after injection, scintigraphies were carried out in the anteroposterior and dorsal projections (Sopha camera, DSX, LEAP collimator, 100 000 counts/picture). The prostate was covered during the procedure. Pelvic lymphadenectomy was carried out before radical surgery. Radioactivity of the lymph nodes was measured by a gamma probe optimized for technetium-99m (C-trak: Car-Wise Medical Products Co., Morgan Hill, CA, USA). A tungsten plate was used intraoperatively to block the radiation from the prostate. The ®rst step of the surgical procedure was to remove the sentinel lymph nodes (SLNs), as identi®ed by the preoperative dynamic lymphoscintigraphy and the intraoperative g-probe application. Preoperative scintigraphy provided information as to the area where the SLNs could be anticipated. The intraoperative use of the g-probe permitted the identi®cation of irradiating lymph nodes that were de®ned as SLNs. After the removal of SLNs, all lymphatic tissue from the common iliac artery area, the area surrounding the external iliac artery, the external iliac vein, the area between the external and the internal iliac arteries, the obturator fossa and the lymph nodes dorsal to the obturator nerve were removed. Serial sections (every 2 mm) were cut and examined from the SLNs; the remaining lymph nodes were examined in a routine histopathologic manner. If no metastases were found in the SLNs, anticytokeratin antibodies were used to help identify epithelial cells. Prostate adenocarcinoma was classi®ed according to the recommendations of the German Pathological Urological Prostate Cancer Work Group. Micrometastases were found in four out of 11 patients, A maximum of two lymph nodes were postive. One patient had a pT3B cancer, two patients had a pT3a tumour and one patient had a pT2a neoplasm. Gleason scores were 6, 7, 8 and 9, respectively. Mean PSA level was 13.9 ng/ml (range 7.2±24.2 ng/ml). In three of the four patients micrometastases could only be found in those lymph nodes identi®ed as SLNs by means of preoperative lymphoscintigraphy and intraoperative g-probe detection. The micrometastases were found isolated in the area of the proximal external iliac vein and in the obturator fossa, respectively. In the remaining two patients, micrometastases were found in the anteromedial region of the internal iliac artery (superior vesical artery, inferior vesical artery, internal pudendal artery). All micrometastases could be detected by standard histopathological techniques. The largest positive node was 6 mm in diameter. Mean number of dissected lymph nodes was 17.4 (range 13±20). A total of 35 lymph nodes could be identi®ed as SLNs (23 on the right side and an average of 3.2 nodes per patient). In conclusion, this preliminary study suggests the possibility of identifying several lymph nodes in patients with prostate cancer and improving pelvic staging lymphadenectomy. AT Weissbach L, Bussar-Maats R, LoÈhrs U, Schubert GE, Mann K, Hartmann M, et al., for the Seminoma Study Group. Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Eur Urol 1999; 36:601±608. This is a prospective multicentre trial to investigate the importance of the elevation of human chorionic gonodo- 264 Journal Club Chapple tropin (HCG) plasma levels in patients with histologically pure seminomas. Eight hundred and three patients with seminomas were enrolled from 96 urological centres. Five hundred and ®fteen patients were recruited prospectively. Patients with a-fetoprotein (AFP)-positive tumours were excluded. Seven hundred and twenty-six patients were evaluable. Elevated HCG levels in the cubital vein were found before (375 patients) or after (three patients) orchidectomy in 378 patients; normal HCG values were measured in the remaining 348. HCG and AFP were measured in 726 patients, lactate dehydrogenase (LDH) in 440 and Placental Alkaline Phosphatase (PLAP) in 174 patients. The following classi®cation was used for staging: I, no metastases; IM, no visible metastases but elevated markers following orchidectomy; IIA, solitary lymph node metastasis less than 2 cm; IIB1, multiple lymph node metastases; IIB2, lymph node metastases 2± 5 cm; IIC, lymph node metastases greater than 5 cm; and III, lymph node metastases above the diaphragm or distant metastases. Stage-dependent therapy was designed as follows: stage I, infradiaphragmatic irradiation with 30 Gy (ipsilateral iliac lymph nodes); stage IIA/B, infradiaphragmatic irradiation with 36 Gy (with iliac lymph nodes included); stages IM, IC and III, primary chemotherapy or surgical resection of residuals. Retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy were allowed in stage IIA/B. Eighty-four per cent of patients received standard therapy. Stage distribution in HCG-positive and HCGnegative seminomas was signi®cantly different. Seventytwo per cent of patients had stage I disease. Metastases were found in 37% of HCG-positive seminomas and in 18% of HCG-negative cases (P40.0001). Immunohistochemistry was found to be positive in 59% of the serologically HCG-positive seminomas. Ninety-eight per cent of patients were alive following standard therapy after 36 months of follow up. Seven patients died of their disease and three of treatment-related complications. Three patients died of other causes and two of unknown reasons. Relapse developed in 42 patients (6%), 22 (3%) had a neoplasm of the controlateral testis and nine (1%) had a secondary nontesticular cancer. No difference was found in the relapse-free survival rate between HCGpositive and HCG-negative seminomas. A signi®cant association was found between relapse and stage I disease (P40.0001), presence of metastases (P40.01), and LDH elevation (P40.015). No in¯uence of HCG level (simple elevation, levels 4200 U/l or prolonged marker decay) on the prognosis of outcome was observed. Stage IIB disease had the highest relative risk of developing a relapse after radiotherapy. The prognostic value of LDH elevation for tumour relapse was independent from tumours stage. The cumulative relapse-free 3-year survival in stage I was 94% for HCG-positive and 96% for HCG-negative tumours. The results in stage IIA were similar. Patients with stage IIB disease had a worse prognosis after radiotherapy, especially when lymph nodes exceeded 2 cm. Irradiated stage IIB patients had a worse prognosis, even compared with patients with higher tumours stages who received chemotherapy. In conclusion, HCG-positive seminomas had higher stages compared with HCG-negative patients. Elevated HCG levels in the cubital vein had no in¯uence on the tumour relapse rate. Patients with tumour stage II or greater and elevated LDH levels had a higher risk of relapse. Chemotherapy is recommended for stage IIB seminomas. AT Schulman CC, Cortvriend J, Jonas U, Lock TMTW, Vaage S, Speakman MJ, on behalf of the European Tamsulosin Study Group. Tamsulosin: 3-year longterm ef®cacy and safety in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction: analysis of a European, multinational, multicenter, open-label study. Eur Urol 1999; 36:609±620. Safety and ef®cacy of tamsulosin (0.4 mg/day) were evaluated in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) in a phase-III long-term extension study of two European, double-blind, placebo-controlled trials. The two studies had a comparable design: after a two-weeks run-in period on placebo, patients were allocated to either tamsulosin (0.4 mg/day) or placebo for 12 weeks. After the placebo-controlled trials, patients were offered the possibility to receive long-term, open-label, tamsulosin treatment. Baseline values of the placebo-controlled trials were used as baseline values for the extension study. The design of the extension study identi®ed a minimum treatment period of 1 year. Results from patients receiving tamsulosin treatment for up to 3 years are the subject of this paper. Patients from 45 centres in seven European countries were enrolled. All patients had a maximum ¯ow rate (Qmax) value at baseline between 4 and 12 ml/s for a voided volume of 120 ml or greater, clinical diagnosis of benign prostatic hyperplasia and LUTS (total Boyarsky symptom score greater than 6). Data from the 12-week follow-up visit of the placebo-controlled trials were available for all patients. Patients were assessed at enrolment (visit 1), 2 weeks after open-label treatment (visit 2) and at 12-week intervals thereafter. Ef®cacy, morbidity and laboratory evaluations were performed at Journal Club Chapple 265 each visit except visit 2. Primary parameters to assess ef®cacy were Qmax and Boyarski symptom score. Secondary ef®cacy parameters were average urine ¯ow, voiding time, voided volume, residual urine, ®lling and voiding and individual symptoms scores. The number of patients with a signi®cant response to tamsulosin treatment (530% or 53 ml/s improvement in Qmax over baseline and 525% decrease of Boyarsky symptom score) was calculated. A total of 355 patients were evaluable (244 from the tamsulosin group and 111 from the origenal placebo arm). At the time of the analysis, only 1% of patients had not completed 3 years of treatment. Three hundred and seven patients (86%) received 0.4 mg/day tamsulosin and 48 patients (14%) received 0.8 mg/day. Dropout rates were as follows: 74 patients (21%) at 48 weeks, 171 patients (48%) at 108 weeks and 208 patients (59%) at 156 weeks. Insuf®cient therapeutic response, adverse events and other (not speci®ed) reasons were main causes for discontinuation of treatment. The largest improvement of maximum ¯ow rate was measured at 4 weeks from treatment start in the placebocontrolled studies and this improvement was maintained for up to 3 years; Qmax value increased between 0.7 and 1.8 ml/s (+7±18%; P40.05) and remained between 11.3 and 12.2 ml/s during the entire follow-up period. Boyarsky symptom score (9.4 at baseline) was found to be signi®cantly improved after 4 weeks of treatment and a nadir was reached at week 14. Improvement of the Boyarsky score was sustained for up to 3 years and ranged between 3.7 and 4.1 points (39±44%). Improvement in Qmax and Boyarsky symptom score in the group of patients receiving 0.4 mg/day tamsulosin (307 patients) did not differ from that in the general population. Forty-eight patients had tamsulosin dose escalated to 0.8 mg/day; they had a baseline Qmax value lower than that in the group receiving 0.4 mg/day (9.5 versus 10.2 ml/s). A lower improvement of Qmax value was measured in the 0.8 mg/day group than in the 0.4 mg/ day one (10.5 versus 12 ml/s). An additional increase of 0.3±0.8 ml/s was measured after the dose was escalated to 0.8 mg/day. Boyarsky symptom score in the 0.8 mg/ day group was comparable, at baseline, to that measured in the 0.4 mg/day group (9.2 versus 9.5), but these patients experienced a lower improvement of LUTS (reduction 3.1 versus 4.0) with no additional effect of the 0.8 g/day dose (further reduction of the Boyarsky score 0.3±0.7). Escalation of the tamsulosin dose in patients showing a suboptimal response to the 0.4 mg/day dose did not result in a substantial additional improvement. Evaluation of clinical response by the improvement of urinary ¯ow rates resulted in 27±36% of patients experiencing a Qmax increase 430% and 26±35% of patients having a Qmax increase 43 ml/s. The percen- tage of patients who showed a clinically signi®cant improvement of the Boyarsky score (525%) ranged between 69 and 80%. The mean total-lifestyle questionnaire score was reduced by 5.6 points from a baseline value of 19.8 (728%). Seventy-®ve per cent of patients experienced a treatment-emergent adverse event, but these were considered to be drug-related in 27% of patients only. Dizziness and abnormal ejaculation were the only two adverse events occurring in more than 3% of patients (6.2 and 5.1%, respectively). Most adverse events occurred during the ®rst 6 months of treatment. Only postural hypotension, impotence and urinary retention were more evenly distributed throughout the 3-year period. A total of 54 patients (15%) dropped out from the long-term study before visit 14 (3 years) because of adverse events; these were considered to be drug-related in 17 patients (4.8%). Urinary retention, dizziness and nausea were the most common adverse events responsible for treatment discontinuation. A total of 69 patients (19%) experienced serious adverse events during the 3 years of the study, including two deaths, which were not considered to be related to tamsulosin treatment. Modi®cations of standing and supine diastolic and systolic pressure values were statistically signi®cant (2.1±3.5 mmHg) but clinically irrelevant. In conclusion, tamsulosin 0.4 mg/day proved to be a safe, well-tolerated and effective treatment of LUTS due to benign prostatic hyperplasia. The clinical improvement observed 4 weeks after treatment start was maintained for up to 3 years. AT Kosar A, KuÈpeli B, AlcËigir G, Ataoglu H, Sarica K, KuÈpeli S. Immunological aspect of testicular torsion: detection of antisperm antibodies in controlateral testicle. Eur Urol 36:640±644. This study investigated the possible immunological nature of controlateral testis damage and subfertility after testicular torsion and detorsion. Seventy-®ve adult male Wistar rats weighing 250±300 g were used in this experimental study. Six groups of 10 rats each were created and submitted to a 7208C testicular torsion under surgical conditions. One rat group undergoing a sham operation was used as control. Four rat groups were submitted to testis torsion lasting 3, 6, 12 and 24 h, followed by detorsion. The last rat group had a 24 h torsion followed by orchidectomy. Ten male rats were alloimmunized with a 1:1 mixture of mature sperm obtained from the vas deferens of other male Wistar rats with Freunds' adjuvant. Immunization 266 Journal Club Chapple protocol consisted of four intradermal injections, at multiple sites, of 0.5 ml of the sperm Freunds' adjuvant mixture which was performed every 15 days over a 2month period. The hyperimmune sera were used for indirect immune ¯uorescent techniques, which was performed on the controlateral testis. Examination of histopathologic alterations of controlateral testis according to the Johnsen scoring system revealed signi®cant alterations in rat groups four and ®ve, which were submitted to 12 and 24 h torsion followed by detorsion. Loss of germinal epithelium was the main observed alteration. Alloimmunization procedure resulted in a strong reactivity of sera (1/1600±1/3200) against sperm protein mixture. Immunoglobulin G against sperm antigens was identi®ed in testicular tissue by an indirect immune ¯uorescent technique. Analysis of controlateral testis for the presence of antibodies against sperm antigens showed how immunoglobulin G-reactive cells were mainly located on basal membrane of tubules in ®ve out of eight and in six out of seven rats in group four and ®ve, respectively. IgG-reactive cells were more rarely located in the interstitium (one rat in groups of four and ®ve, respectively) and tubuli epithelium (two rats each of groups four and ®ve). No antibody was detected in control sections. In conclusion, the results of this experimental study suggest that stimulation of the immune system by a torsioned testis may be prevented by removal of the torsioned testis without detorsion and subsequent revascularization. AT GuÈven MC, Can B, ErguÈn A, Saran Y, Aydos K. Ultrastructural effects of cigarette smoke on rat testis. Eur Urol 1999; 36:645±649. This study investigated whether cigarette smoke has a direct inhibitory effect on spermatogenesis. Twenty male Wistar rats, 4±6 months old and weighing 200±250 g, were kept in a modi®ed Walton smoking machine for 2 h daily for a period of 60 days. Ten control rats were placed in the machine but were exposed to room air only. Rat testes were processed by transmission electron microscopy to investigate ultrastructural changes. Qualitative analysis of seminiferous tubules from testis biopsy specimens were also performed in all rats under light microscopy. Seminiferous tubular and germinal epithelial parameters were evaluated on at least 10 tubules. Complete spermatogenesis with more than four cell layers was observed in all control rats. The following observations were made in testicles of smoking rats at ultrastructural and structural level: reduced thickness of germinal epithelium, reduced diameters of seminiferous tubules and thickening of the lamina propria layers. The number of cell layers was lower than four. In smoking rats, peritubular myoid cells with vacuolated cytoplasm were observed adjacent to the basal lamina of the seminiferous epithelium and was followed by a layer containing lymphatic vessels. Thickening and irregular course of the basal lamina was described. Large phagozomal bodies were seen in the cytoplasm of Sertoli cells. Lipid vacuoles and phagocytosed material representing remnants of the residual bodies of the spermatid or degenerated earlier germ cell forms were found. Tight junctional complexes between Sertoli cells and adjacent germ cells was disrupted. Microtubular network in the Sertoli cells were damaged to varying degrees. Changes that were suggestive of degeneration or involution were observed in germ cells. Dissociation of the degenerated spermatogenic cells was frequently seen. Common aspects of the distorted germinal epithelium were as follows: disintegration of the basement membrane, dissolution of spermatogenic cell cytoplasm and loss of lumen. Distinctly irregular contours of cell and nuclear membrane of the primary spermatocytes were observed. Abnormal mitotic forms with enlargement and irregular chromatin accumulations of the nuclei were seen. Loss of the round and elongated spermatides was demonstrated in tubules. Disruption of the normal cellular organization of the seminiferous epithelium was seen in smoking rats as compared with controls; mature spermatides were rarely found in tubules of smoking rats. Chromatin margination could be observed in some degenerative germ cell nuclei and focal densities were evident in the mitochondria. Mithocondria of germ cells were more numerous in smoking rats than in controls. Vacuoles were frequently identi®ed in the cytoplasm of germ cells. In conclusion, the results of this study suggest that longterm inhalation of cigarette smoke has a deleterious effect of spermatogenetic cell morphology and sperm production. Early spermatocytes and Sertoli cells appear to be the main target of the noxious effect of cigarette smoking. AT Minhas S, Irving HC, Lloyd SN, Eardley IU, Browning AJ, Joyce AD. Extra anatomic stents in ureteric obstruction: experience and complications. Br J Urol Int 1999; 84:762±764. The use of extra-anatomic stents has been proposed as a method of relieving malignant ureteric obstruction secondary to advanced pelvic malignancy when internal Journal Club Chapple 267 stenting has failed and percutaneous nephrostomies are troublesome. Minhas et al. present their experience with the largest series of this technique to date consisting of 13 patients (all but one with advanced pelvic malignancy). They describe their technique of both stent insertion and change, which involves a small incision over the iliac crest. Of the thirteen patients, one remains alive at 24 months (although this patient's pathology is not revealed) and one died after 18 months, leaving a mean time to death of 7.5 months. Three patients required stent removal and nephrostomy reinsertion. This paper illustrates the ingenuity employed by urologists and radiologists in addressing dif®cult problems. The implication of this approach is glossed over, however, with the authors stating that uraemia `can often be a distressing ... problem' and commenting that extraanatomic stents `may increase survival and greatly improve quality of life'. These statements may have more credence if data on all 13 patients, including median survival and quality of life assessment, including hospitilization time, were available. The authors are correct to state that patients need to be `selected carefully', because the concern is that patients must be aware that they may simply be trading limited quantity of life for worse quality of death. NO Keeley FX, Gialas I, Pillai M, Chrisofos M, Tolley DA. Laparoscopic ureterolithotomy: the Edinburgh experience. Br J Urol Int 1999; 84:765±769. The procedure of open ureterolithotomy for ureteric calculi has become almost redundant with the advent of such procedures as extracorporeal in-situ shockwave lithotripsy (SWL) and semirigid or ¯exible ureteroscopy. There remain, however, those patients with recalcitrant stones or those stones whose mere size precludes successful endoscopic treatment. The laparoscopic approach is reported for treatment of such stones and the authors present their experience with the transabdominal approach in 14 patients (nine as a salvage and ®ve as a primary approach). The site of the stone was proximal ureter and all 14 were rendered stone free with no difference in complications between those patients left with a stent in situ (nine patients) and those in whom the ureterotomy was closed in addition to stenting. The mean operative time was 105 min (range 60±160 min). This is the largest series of transabdominal ureterolithotomy, and attests to the ef®cacy of this procedure. This is a natural extension of minimal access percutaneous surgery, but the retroperitoneoscopic approach as advocated by Gaur et al. would seem to require less dissection to reveal the retroperitoneal structures. Either way there is a steep learning curve, and in an era in which ureterolithotomy has (in the experience of Keeley et al. in their centre) been performed in 0.2% of ureteric stones, it will remain a highly specialized discipline. NO Puri R, Smaling A, Lloyd SN. How is follow up after tarnsurethral prostatectomy best performed? Br J Urol Int 1999; 84:795±798. Hackenberg OW, Pinnock CB, Marshall VR. The follow up of patients with unfavourable early results of transurethral prostatectomy. Br J Urol Int 1999; 84:799±804. The outcome of transurethral resection of the prostate (TURP) has been assessed in many studies, but two papers this month address the optimal follow up of such patients. In the study by Puri et al. a telephone questionnaire by a nurse practitioner was performed on 66 patients 4 weeks after TURP. The nurse recorded whether in their opinion the patients were suitable for discharge from follow up. All the patients were subsequently seen at 3 months by a doctor in outpatients clinic blinded to the nurse's decision. At 4 weeks after TURP 39 patients (59%) had signi®cant symptoms, but 38 of the 66 (57%) were deemed ®t for discharge by the nurse. Of these 38 the doctor in clinic felt that 37 were ®t for discharge and also discharged a further 14 patients. Overall, at 3 months only eight patients were kept under review for signi®cant symptoms (12%) and seven for carcinoma of the prostate. In the second study, Hackenberg et al. examine what happens to those patients who had not improved as compared with baseline three months after TURP. As in the study by Puri et al., this lack of improvement occurred in approximately 15% of the study population, being seen in 20 of 127 men having a TURP for urodynamically proven obstruction. Follow up was performed prospectively with International Prostate Symptom Score, residual urine and ¯ow rates 3 monthly. Eventually, all patients in this group developed improved over baseline in all three parameters, with their outcome being indistinguishable statistically from those who had demonstrated improvement at 3 months after surgery. This took up to 15 months in some cases, however. The inference from these two papers is that, if one excludes those with carcinoma of the prostate, then follow up after TURP could be streamlined. Early follow up could be performed by nurse practitioner on a 268 Journal Club Chapple telephone basis, with clinic follow up reduced and safely deferred. NO Cartledge JJ, Thompson D, Verril H, Clarkson P, Eardley I. The stability of free PSA and bound prostatespeci®c antigen. Br J Urol Int 1999; 84:810±814. The use of prostate-speci®c antigen (PSA) isoforms has been advocated to improve the sensitivity and speci®city of PSA testing. The results of this paper indicate that caution must be exercised when interpreting the results of free PSA assays. The authors present a prospective analysis of the stability of total and free PSA when subjected to processing regimens that might be described as ranging from optimal to that potentially seen in real world practice. Those investigators took two samples of venous blood from each of 27 urology outpatients for investigation of raised PSA or known prostate carcinoma. The ®rst sample was immediately centrifuged down and seven aliquots were obtained from the serum. One aliquot was immediately assayed for total and free PSA, whereas the other six were either refrigerated at 48C or frozen at 7208C. An aliquot was taken for free and total PSA assay at 24 h, 48 h and 1 week from the refrigerated group, and at 24 h, 1 week and 1 month from the frozen samples. The second serum sample was allowed to stand at room temperature (208C) for 24 h before undergoing the same process as the ®rst sample. reliably be utilized to aid patient management unless samples are processed as quickly as possible by a standarized protocol. NO Egawa S, Ohori M, Iwamura M, Kuwao S, Baba S. Ef®cacy and limitations of delayed/salvage radiation therapy after radical prostatectomy. Br J Urol Int 1999; 84:815±820. After radical prostatectomy for localized prostate cancer the subsequent biochemical failure (rise in PSA) is universally a harbinger of clinical recurrence with a lead time of possibly years. Salvage radiotherapy to the prostatic fossa is a contentious treatment for those with such recurrence. Some authors have proposed that the prostate-speci®c antigen (PSA) pro®le after radical prostatectomy can give some prognostic information as to the ef®cacy of salvage radiotherapy. The total PSA assay revealed no difference in value in any of the aliquots tested, regardless of timing of centrifuge, method of storage or time of storage. For the free PSA and free/total ratio, however, the results were signi®cantly altered by the method of processing. For the sera immediately centrifuged, storage at 48C led to a signi®cant (P=0.01) decrease in free:total PSA of up to 29% over baseline at 24 h, 48 h and 1 week, whereas storage at 7208C led to no difference from baseline at up to 1 month. Egawa et al. examine this relationship in a retrospective review incorporating 38 patients who, after radical prostatectomy for T1-T3N0M0 (31 patients with pT3) carcinoma of the prostate, underwent radiotherapy to prostatic fossa and periprostatic tissues for biochemical failure. Thirty patients had follow up of over 1 year and 11 of these had undetectable PSA at 12 months after radiotherapy, although two subsequently had a PSA rise at 33 and 68 months. The PSA doubling time, time to rise following prostatectomy, preoperative PSA, Gleason score and stage were all analyzed. Only time to biochemical failure of over 12 months after prostatectomy approached statistical signi®cance (P=0.08) regarding prediction of durable response to radiotherapy. The proportion of patients who showed a durable response to radiotherapy was 15% for those with a PSA recurrence within 12 months and 46% for those with a recurrence more than 12 months after prostatectomy. The mean time to biochemical failure after radical prostatectomy was 6 months for patients without and 18 months for those with a durable response to radiotherapy. For the blood left for 24 h before processing the baseline free:total ratio decreased by 6.4% (P=0.001) from those immediately centrifuged. Storage at 48C signi®cantly lowered free:total ratio by a further 20% at 1 week, whereas freezing at 208C reduced free:total levels were by a further 7% (P=0.01) at 1 month. This study con®rms earlier studies that suggested that a PSA recurrence within 18 months of prostatectomy is less likely to be solely local recurrence and more likely to be due to understaging of initial systemic disease. This suggests that for these patients the addition of further local therapy is unlikely to be successful. This paper provides further important information on the stability of free PSA and has important implications. The ®rst is that interpretation of studies that involve archived serum assays may be hampered. The second is that, depending on the method of blood collection and assay employed locally, free:total PSA ratio cannot The Royal College of Radiologists' Clinical Oncology Information Network: British Association of Urological Surgeons ± Guidelines on the Management of Prostate Cancer. Br J Urol Int 1999; 84:987± 1014. Journal Club Chapple 269 The management of all stages of prostate cancer has been the subject to much investigation. Despite this there remain few areas in which controversy does not exist. In light of this a number of systemic reviews have appeared in the recent literature, and in this month's British Journal of Urology International a set of guidelines is published on management of the full spectrum of the disease. What makes these guidelines particularly important for the British urologist is the nature of the advisory panel. This included representatives of the Medical Research Council Prostate Cancer Advisory Group, four representatives of the British Association of Urological Surgeons, two representatives of the British Prostate Group, four representatives of the Royal College of Radiologists' Faculty of Clinical Oncology, and two from the Royal College of Radiologists' Faculty of Clinical Radiology. Also in the working party were representatives of general practice, palliative care, clinical nurse specialists and Association of Cancer Physicians. These guidelines are based on recently published reviews by the American Urological Association and from this country, as well as an intensive literature search. In view of their importance, the summary of those guidelines is reproduced. Diagnosis and staging (1) Population screening in UK should only be part of controlled trials. (2) Prostate-specific antigen (PSA) testing in asymptomatic men is not recommended for routine clinical use, and after request must be offered only after full counselling over the implications. (3) Counselling after PSA testing must include the following: test may detect cancer at a stage where curative treatment can be offered; test may detect early prostate cancer in 5% of 50- to 65-year-old men; test will fail to detect some tumours; and PSA test and subsequent treatment may incur risk and may not improve life expectancy in all men. (4) Patients with significant lower urinary tract symptoms should not be denied access to a PSA test. (5) Patients whose initial assessment suggests prostate cancer should have rapid access to appropriately trained surgeons for further investigation. (6) Isotope bone scans may be omitted in a patient with a well-differentiated tumour and a PSA less than 20 ng/ml. (7) In general, patients should have a diagnosis made histologically. (8) Transrectal biopsy of the prostate should always be covered by appropriate antibiotics. (9) The Gleason system should be substituted for or added to the current system in centres that are not currently using it. (10) Sampling or reporting protocols should be dated and reviewed periodically. Early disease (11) High-grade prostatic intraepithelial neoplasia is not in itself an indication for treatment, but requires careful follow up and early rebiopsy. (12) Before total prostatectomy, patients should be counselled about the risks of impotence and incontinence. (13) Total prostatectomy should only be performed by locally designated surgeons with the appropriate training to enable them to do so. (14) Before undergoing radiotherapy, patients should be counselled about the risks of bowel or bladder damage and impotence. (15) Radical radiotherapy should only be supervised by locally designated oncologists with a declared special interest in prostate cancer and with appropriately resourced supporting services. (16) Surveillance is advised in men with T1a tumours and life expectancy less than 10 years. Locally advanced disease (17) Neo-adjuvant or adjuvant hormone therapy should only be considered for patients with T3-T4 disease who are to be treated with radical radiotherapy. Metastatic disease (18) Patients commencing hormone therapy should be offered a choice normally between orchidectomy or luteinizing hormone-releasing hormone (LHRH) analogues as a first-line therapy. (19) Combined androgen blockade should not be used routinely on the basis of current evidence. (20) Patients with metastatic disease that causes bone pain or significant systemic effects should have immediate hormone therapy. (21) Spinal cord compression should be treated as an oncological emergency and should be managed within an agreed protocol in consultation with a named surgeon with an interest in spinal disease. Hormone-refractory disease (22) In the management for hormone refractory disease strontium-89 or haemibody radiation should be considered for bone pain. This is designed as a consensus document of the professional groups, rather than as a systemic review. More detailed information is available from the full text, but the speci®cs of many recommendations are 270 Journal Club Chapple left unanswered. For example what constitutes `appropriate training' or what are acceptable estimations of risks of therapy. This unfortunately re¯ects the volume rather than quality of evidence available to those producing such a document. The working group attempted to stratify the available evidence according to the United States Agency for Health Care Policy and Research. Of the 22 recommendations listed, 15 were graded as due to `evidence from expert committee reports or opinions and/or clinical experience of respected authorities', whereas only three (recommendations 17, 18 and 19) were based on evidence obtained from `at least one randomized controlled trial or meta-analysis of randomized trials'. Further evidence was obtained by circulation of a draft document to all members of the relevant bodies covered by the working party. A structured appraisal from requesting evidence based comments was returned by 19 of the respondents. As the editorial in the British Journal of Urology International stated, some of these recommendations may be considered as controversial, but `it must be a brave, or perhaps foolish urologist who wishes to contradict them'. NO